Li H, Witte D P, Branford W W, Aronow B J, Weinstein M, Kaur S, Wert S, Singh G, Schreiner C M, Whitsett J A
Division of Basic Science Research, Children's Hospital Research Foundation, Cincinnati, OH.
EMBO J. 1994 Jun 15;13(12):2876-85. doi: 10.1002/j.1460-2075.1994.tb06582.x.
We present an initial characterization of the murine Gsh-4 gene which is shown to encode a LIM-type homeodomain. Genes in this category are known to control late developmental cell-type specification events in simpler organisms. Whole mount and serial section in situ hybridizations show transient Gsh-4 expression in ventrolateral regions of the developing neural tube and hindbrain. Mice homozygous for a targeted mutation in Gsh-4 suffer early postnatal death resulting from immature lungs which do not inflate. Prenatal administration of progesterone and glucocorticoid, to extend gestational term and accelerate maturation, resulted in lung inflation at birth. Nevertheless, the hormonally treated mutants generally failed to survive beyond an hour after birth, due to ineffective breathing efforts. It is concluded that Gsh-4 plays a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.
我们展示了小鼠Gsh - 4基因的初步特征,该基因被证明编码一种LIM型同源结构域。已知这类基因在更简单的生物体中控制晚期发育细胞类型的特化事件。整体标本和连续切片原位杂交显示,Gsh - 4在发育中的神经管和后脑的腹外侧区域有短暂表达。Gsh - 4基因靶向突变的纯合小鼠在出生后早期死亡,原因是肺部不成熟无法充气。产前给予孕酮和糖皮质激素以延长妊娠期并加速成熟,导致出生时肺部充气。然而,经激素处理的突变体通常在出生后一小时内无法存活,因为呼吸努力无效。结论是,Gsh - 4在呼吸控制机制的发育以及肺的正常生长和成熟中起关键作用。